This is a continuation of work begun 2 years ago aimed at obtaining a better understanding of papilledema through a comprehensive, clinical and pathologic study of this condition in man and in experimental animal models. The clinical course the pathologic changes, the pathogenetic mechanisms, the prognosis and treatment of this condition have been investigated with clinical, histopathologic, ultrastructural and pathophysiologic methods. We propose to continue to examine the pathology and pathophysiology of edema of the optic disc in 4 models of papilledema: (1) by irradiating the occipital lobe, (2) by implantation and inflation of intracranial balloon, (3) by ocular hypotony following cyclocryotherapy, (4) by combination of the above methods. By combining experimental models which involve alteration of intracranial pressure and intraocular tension, we hope to study the basic pathophysiologic mechanisms affecting the integrity of the optic disc. In each of these experimental models, the disruption of axoplasmic transport of the optic disc and the circulatory dynamics as studied by fluorescein angiography and horseradish peroxidase will be examined and correlated. The relationship of the integrity of the neuronal elements of the optic disc and the vascular permeability will be explored. Pathologic materials from patients with edema of optic disc will be studied and correlated with clinical findings. These observations will be compared with the experimental models. With a multidisciplinary approach using methods of clinical ophthalmology and experimental pathology including experimental surgery, fluorescein angiography, histopathology, electron microscopy, EM histochemistry, radioautography, we propose to study edema of the optic disc.